Adhesive anastomosis connection system

ABSTRACT

A method of performing an anastomosis, comprising, juxtaposing two blood vessels to be anastomosed using an juxtaposition device, to a desired configuration in which at least one vessel is an end vessel; applying an adhesive to said vessels while they are in said configuration, said adhesive being sufficient to ensure both sealing and bonding of said two vessels to each other, and removing said juxtaposition device after said adhesive sufficiently sets.

RELATED APPLICATIONS The present application claims the benefit under119 (e) of U.S. Ser. No. 60/426,013, filed on Nov. 14, 2002. Thedisclosure of which is incorporated herein by reference. BACKGROUND OFTHE INVENTION

The problem of attaching two blood vessels is well known. While the goldstandard is suturing, various connectors for attaching blood vesselshave recently become more common.

U.S. Pat. No. 5,797,920 to Kim DuckSoo, describes a connector which isbuttressed using an application of a tissue adhesive.

Tissue adhesives in general have found application in various types ofsurgical treatments, for example, surface cuts, GI tract procedures andsmall blood leaks near the heart.

U.S. Pat. No. 6,245,083 to Black, the disclosure of which isincorporated herein by reference, describes a device for apposing twoside-by-side blood vessels for anastomosis. Bio-adhesive is then appliedto the outside of the vessels. While the patent suggests that the methodcan be used for other types of connections, it is not clear how thissuggestion can be carried out, as there is apparently no support in thedisclosure and the procedures disclosed would not work for thatsuggestion. In addition, the adhesive is applied by a separate meansfrom the apposition device.

U.S. Pat. No. 5,725,551 to Myers, et al teaches an adhesive based methodfor sealing punctures in blood vessels.

SUMMARY OF THE INVENTION

A broad aspect of some embodiments of the invention relates toperforming anastomotic connections using an adhesive. In an exemplaryembodiment of the invention, the resulting connection is either a sideto end or end to end connection. In some embodiments of the invention, ascaffold is used during the procedure, for example to ensure that thevessels are properly located with respect to each other, but may beremoved and/or dissolve later and/or serve little or no structuralpurpose once the adhesive has set. Optionally, a connector is provided,to work in conjunction with the adhesive. Optionally, the adhesive isused to protect against possible shortcomings of the connector. Forexample, the connector may provide initial strength and the adhesivelong term strength and/or sealing. Optionally, a combined scaffoldingand adhesive delivery system is used to hold the vessels and apply theadhesive.

In exemplary embodiments of the invention, an adhesive provides one orboth of the following functions, bonding the two vessels and sealing theattachment area between the vessels. In an exemplary embodiment of theinvention, the adhesive both bonds and seals.

In an exemplary embodiment of the invention, an anastomosis scaffoldingcomprises a scaffolding, such as one or more wires which are pulledthrough the adhesive, before, during or after the setting of theadhesive. This scaffolding may be, for example outside the blood vessel,optionally piercing one or both blood vessels.

Alternatively or additionally, an anastomosis scaffolding comprises asupport inside a blood vessel, for example one or more inflatable orexpandable structures such as balloons.

In an exemplary embodiment of the invention, an adhesive delivery systemremains outside of the lumens of the blood vessels being attached.Optionally, any scaffolding also remains outside of these lumens.

In an exemplary embodiment of the invention, the device scaffolding isdesigned to support a range of angles between the two blood vessels(e.g., including grafts) that are being attached to each other.

An aspect of some embodiments of the invention relates to an anastomosisconnection system, adapted to connect a side vessel to an end vesselusing adhesive. In an exemplary embodiment of the invention, the systemincludes an internal scaffold, for example a balloon and/or a deployableelement. Optionally, the internal scaffold is inserted through anincision one of the blood vessels, which may later be sealed, ifrequired.

An aspect of some embodiments of the invention relates to an end to endanastomosis system, using adhesive, in which any scaffold is external tothe blood vessels being attached to each other. In an exemplaryembodiment of the invention, the system comprises two vessel holders,each of which holds one vessel, optionally with everted lips. The twoholders are then brought together and the connection made, for exampleby application of adhesive.

An aspect of some embodiments of the invention relates to an anastomosissystem including pullers for pulling and holding two blood vessels to beconnected and an adhesive applicator to apply an adhesive to theanastomosis area.

A broad aspect of some embodiments of the invention relates totechniques for adhesive based anastomosis. In an exemplary embodiment ofthe invention, an anastomosis adhesive system includes one or moreblowers, which may be used, for example, to dry an area in preparationfor adhesive application and/or for assistance in setting the adhesive.

In an exemplary embodiment of the invention, the adhesive systemincludes one or more nozzles, for example a ring array of nozzles.Optionally, the nozzles are used for controlled application of adhesive.In an exemplary embodiment of the invention, the nozzles are arranged topreferentially provide more adhesive at one side than another, forexample if an oblique anastomosis is performed and/or depending at theinstant angle at the area of application between the two vessels.

Optionally, adhesive shaping is provided using a form that controls theextent of adhesive flow. Optionally, a flow limiter is provided, whichprevents overflow of adhesive to adjacent tissue. Such a flow limitermay include, for example, a collar and/or a tissue protector pad.

In an exemplary embodiment of the invention, means for removing bubblesfrom an adhesive globule is provided, for example, one or more thinneedle nozzles attached to a suction source. Optionally, the needles areprovided in the path of adhesive between a delivery nozzle to ananastomosis area and/or inside the anastomosis area.

Optionally, a foaming means is provided, for example a gas source to bemixed in with the adhesive or a specially shaped nozzle. Such foam mayadhere better and/or dry better.

In an exemplary embodiment of the invention, a primer layer is appliedprior to applying adhesive, for example on an adventisia part and/or onan intima part of blood vessels. Different primers may be provided fordifferent tissue types. Optionally, a hardener is provided after theadhesive. Optionally, different nozzles and/or sets of nozzles are usedfor different applied materials. If a binary adhesive is used, thebinary components may share a single nozzle and/or supply tube or bemixed after application. Optionally, one or more of the adhesivecompounds, adhesives area and/or other delivered materials are heated bythe anastomosis system, for example, to hasten setting.

In an exemplary embodiment of the invention, the delivery systemutilizes electrical and/or mechanical mechanism for timing the operationof the system, for example application of adhesive, blow drying andrelease of the completed connection after the adhesive is sensed and/orestimated to be dry. Optionally, a visual marker is used, for example aslowly oxidizing dye, which changes color after a set time periodcorresponding to the setting time of the adhesive, so that an operatorcan determine if a scaffolding may be removed.

A particular feature of some embodiments of the invention which may makethem easier to use is that blood flow can continue during the adhesivesetting time and/or the vessel attachment time.

An aspect of some embodiments of the invention relates to holding an endof a vessel open, from the outside, using vacuum, for example using oneor more vacuum nozzles arranged adjacent its circumference at one end.Optionally, the nozzles, when activated, maintain the vessel in aneverted or semi-everted position.

An aspect of some embodiments of the invention relates to a method ofattaching two vessels in which one or more scaffold elements, forexample one or more wires, are adhered, for example using an tacky glueto the outside of one or both vessels. Then the vessels are attached,for example using adhesive, and the wires pulled out. Alternatively oradditionally, the wires are hooked into the vessel(s).

In an exemplary embodiment of the invention, the wires are coated with amaterial that at least partially resists adhesion by the adhesive.Optionally, the wires are heated or vibrated to assist their removal.

An aspect of some embodiments of the invention relates to using aninternal shunt as a scaffolding for an adhesive anastomotic procedure.Optionally, the shunt is somewhat stiffened, to ensure that it holds thevessels. Unlike standard shunts for anastomosis, in which a region isprovided near the anastomosis area for needle maneuvers, in an exemplaryembodiment of the invention, the shunt fills the blood vessels at theanastomotic area, to provide support. As the anastomosis is performed byapplying an adhesive outside the blood vessels, in some embodiments ofthe invention the shunt does not interfere with needle manipulation ofvessel manipulation, as they are not needed.

There is thus provided in accordance with an exemplary embodiment of theinvention, a method of performing an anastomosis, comprising:

juxtaposing two blood vessels to be anastomosed using an juxtapositiondevice, to a desired configuration in which at least one vessel is anend vessel;

applying an adhesive to said vessels while they are in saidconfiguration, said adhesive being sufficient to ensure both sealing andbonding of said two vessels to each other; and

removing said juxtaposition device after said adhesive sufficientlysets. Optionally, juxtaposing comprises engaging at least one of saidvessels using said juxtaposition device

In an exemplary embodiment of the invention, juxtaposing comprisesinserting at least a portion of said juxtaposing device into at leastone of said vessels.

In an exemplary embodiment of the invention, juxtaposing comprisesinserting at least a portion of said juxtaposing device into a wall ofat least one of said vessels.

In an exemplary embodiment of the invention, juxtaposing comprisesjuxtaposing by manipulating said juxtaposing device. Optionally,juxtaposing comprises pulling at least one of said vessels using saidjuxtaposing device.

In an exemplary embodiment of the invention, juxtaposing comprisesjuxtaposing said vessels to have substantially no space between thevessels at an anastomotic location thereof. Optionally, juxtaposingcomprises juxtaposing said vessels to have a sealed contacttherebetween.

In an exemplary embodiment of the invention, juxtaposing comprisesproviding at least one of said vessels using a graft delivery system andwherein said juxtaposition device is coupled to said graft deliverysystem.

In an exemplary embodiment of the invention, applying an adhesivecomprises applying an adhesive to said juxtaposition device.

In an exemplary embodiment of the invention, applying an adhesivecomprises not applying an adhesive to said juxtaposition device.

In an exemplary embodiment of the invention, the method comprises dryingan anastomosis area of said blood vessels using a stream of air, priorto said applying.

In an exemplary embodiment of the invention, the method comprisesassisting a setting of said adhesive. Optionally, said assistingcomprises blowing air on said adhesive. Optionally, said air is heated.

In an exemplary embodiment of the invention, applying comprises mixingan adhesive from at least two components during a process of flowingsaid adhesive during said applying.

In an exemplary embodiment of the invention, applying comprises applyingusing at least one nozzle.

In an exemplary embodiment of the invention, applying comprises applyingusing a plurality of nozzles arranged in a ring.

In an exemplary embodiment of the invention, applying comprises applyinginto a mold adjacent said anastomosis area, which mold shapes theadhesive about said area

In an exemplary embodiment of the invention, applying comprises into aform adapted to inhibit spillover.

In an exemplary embodiment of the invention, applying comprises applyinga pre-measured amount of adhesive.

In an exemplary embodiment of the invention, applying comprises applyingas a continuous flow.

In an exemplary embodiment of the invention, the method comprisesremoving some of said adhesive after said applying.

In an exemplary embodiment of the invention, said removing comprisesremoving after said adhesive sets completely.

In an exemplary embodiment of the invention, said removing comprisesremoving before said adhesive sets completely.

In an exemplary embodiment of the invention, said removing comprisesremoving as soon as said adhesive starts to set.

In an exemplary embodiment of the invention, said removing comprisesremoving before said adhesive starts to significantly set.

In an exemplary embodiment of the invention, said applying comprisesapplying while blood flows in at least one of said blood vessels.

In an exemplary embodiment of the invention, no foreign materials otherthan said adhesive remain in said anastomosis.

In an exemplary embodiment of the invention, the method comprisesproviding at least one strengthening element in said anastomosis andleaving said at least one strengthening element permanently in saidanastomosis.

There is also provided in accordance with an exemplary embodiment of theinvention, a method of performing an anastomosis, comprising:

attaching at least a first scaffold element to a first blood vessel;

attaching at least said first scaffold element or a second scaffoldelement to a second blood vessel;

positioning said blood vessels using said at least a first scaffoldelement, to a desired configuration;

applying an adhesive to said vessels while they are in saidconfiguration, said adhesive being sufficient to ensure both sealing andbonding of said two vessels to each other; and

removing said at least first scaffolding element.

In an exemplary embodiment of the invention, said first blood vessel isa side vessel. Alternatively, said first blood vessel is an end vessel.

In an exemplary embodiment of the invention, the method comprisesmechanically attaching said at least first scaffolding element to saidfirst blood vessel. Optionally, mechanically attaching comprisespiercing. Alternatively or additionally, mechanically attachingcomprises hooking.

In an exemplary embodiment of the invention, the method comprisesadhesively attaching said at least a first scaffolding element to saidfirst blood vessel. Optionally, the method comprises adhesivelyattaching using a tacky adhesive.

In an exemplary embodiment of the invention, the method comprisesattaching a second scaffolding element to said second blood vessel.

In an exemplary embodiment of the invention, a same first scaffoldingelement is attached to both of said blood vessels.

In an exemplary embodiment of the invention, said at least onescaffolding element comprises a plurality of wires.

In an exemplary embodiment of the invention, said at least onescaffolding element comprises a shunt.

In an exemplary embodiment of the invention, said at least onescaffolding element comprises a balloon.

In an exemplary embodiment of the invention, positioning comprisesdirect manual positioning.

In an exemplary embodiment of the invention, positioning comprisespositioning by manipulating said at least one scaffolding.

In an exemplary embodiment of the invention, positioning comprisespositioning said vessels to have substantially no space between thevessels at an anastomotic location thereof.

In an exemplary embodiment of the invention, applying an adhesivecomprises applying an adhesive using a port coupled to said at least onescaffolding element.

In an exemplary embodiment of the invention, applying an adhesivecomprises applying an adhesive into a form which shapes said adhesiveabout said configuration.

In an exemplary embodiment of the invention, the method comprisesblowing air on said adhesive to aid setting.

In an exemplary embodiment of the invention, removing comprises removingsaid at least one scaffolding element after said adhesive sets.

In an exemplary embodiment of the invention, removing comprises removingat least one of said at least one scaffolding elements before saidadhesive sets.

There is also provide din accordance with an exemplary embodiment of theinvention, apparatus comprising:

an adhesive source;

at least one adhesive delivery port;

at least one blood vessel holder adapted to stabilize said port relativeto an anastomosis area of two blood vessels.

In an exemplary embodiment of the invention, said vessel holder isadapted to remain external to said vessels.

In an exemplary embodiment of the invention, said vessel holder isadapted to penetrate at least one of said vessels.

In an exemplary embodiment of the invention, said vessel holder isadapted to penetrate both of said vessels.

In an exemplary embodiment of the invention, said vessel holdercomprises a plurality of wires adapted to engage a blood vessel.

In an exemplary embodiment of the invention, said vessel holdercomprises a vacuum source which applies vacuum to an outside of avessel, thereby holding it.

In an exemplary embodiment of the invention, the apparatus comprises arim adapted to inhibit spillover of adhesive.

In an exemplary embodiment of the invention, said apparatus defines aform between said apparatus and said blood vessels, for filling withadhesive and shaping a desired set adhesive configuration.

In an exemplary embodiment of the invention, said at least one deliveryport comprises a plurality of ports adapted to be arranged around one ofsaid vessels

In an exemplary embodiment of the invention, said at least one deliveryport comprises a structure adapted to mix at least two components of anadhesive.

In an exemplary embodiment of the invention, said at least one deliveryport comprises at least one nozzle attached to a first component sourceof adhesive and at least one nozzle attached to a second componentsource of adhesive.

In an exemplary embodiment of the invention, the apparatus comprises asource of gas adapted to be aimed at said anastomosis area.

In an exemplary embodiment of the invention, the apparatus comprisesmeans for assisting setting of said adhesive.

In an exemplary embodiment of the invention, the apparatus comprises aheater for said gas.

In an exemplary embodiment of the invention, the apparatus comprises asetting sensor which provides an indication of setting of said adhesive.

In an exemplary embodiment of the invention, the apparatus comprises asetting timer.

In an exemplary embodiment of the invention, the apparatus comprises acontroller which synchronizes a an activation of said vessel holder anddelivery of said adhesive. Optionally, said controller is a mechanicalcontroller using mechanical means to determine said synchronization.Alternatively, said controller is an electrical controller usingcircuitry to determine said synchronization.

In an exemplary embodiment of the invention, said apparatus is mountedin a delivery capsule adapted to be attached to a delivery system andadapted to hold a graft vessel therein.

In an exemplary embodiment of the invention, said capsule includes a setamount of adhesive. Alternatively or additionally, said capsule includesa single external control.

In an exemplary embodiment of the invention, said vessel holder isarranged to be split after use.

In an exemplary embodiment of the invention, said vessel holder includesa slot in a side thereof, adapted for placement of a vessel therein.Optionally, said slot is fixed.

There is also provided in accordance with an exemplary embodiment of theinvention, an adhesive anastomotic system, comprising:

a first blood vessel holder;

a second blood vessel holder adapted to interlock with said first bloodvessel holder, such that blood vessels held by said two vessel holderscontact; and

an adhesive port configured to deliver an adhesive to said contact.

Optionally, said vessel holders are configured to hold two vessels in anend-to-end configuration.

There is also provided in accordance with an exemplary embodiment of theinvention, apparatus comprising:

an adhesive source;

at least one adhesive delivery port;

at least one vessel holder mechanically coupled to said delivery portand adapted to stabilize said port relative to at least one bloodvessel; and

an adhesive setting enhancer. Optionally, said enhancer comprises asource of gas. Alternatively or additionally, said enhancer comprises asource of energy.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary, non-limiting embodiments of the invention will be describedbelow, with reference to the following figures, in which the sameelements are marked with the same reference numbers in differentfigures:

FIG. 1 is a flowchart of a method of performing an adhesive-basedanastomosis, in accordance with an exemplary embodiment of theinvention;

FIGS. 2A-2G are a series of illustrations showing various stages in theapplication of the method of FIG. 1 to a side to end anastomosis;

FIG. 3 is a schematic illustration of a vacuum based graft deliverysystem, in accordance with an exemplary embodiment of the invention;

FIGS. 4A-4E illustrate hook-based scaffolding, in accordance with anexemplary embodiment of the invention;

FIGS. 5A-5C illustrate adhesive-based scaffolding, in accordance with anexemplary embodiment of the invention;

FIG. 6 is a schematic illustration of an adhesive delivery system, inaccordance with an exemplary embodiment of the invention;

FIG. 7 shows an adhesive delivery system including a rim, in accordancewith an exemplary embodiment of the invention.

FIGS. 8A-8E show various attachment configurations of blood vessels, inaccordance with exemplary embodiments of the invention;

FIGS. 9A and 9B show a method of achieving the configuration of FIG. 8C,in accordance with an exemplary embodiment of the invention;

FIGS. 10A and 10B show a method of achieving the configuration of FIG.8E, in accordance with an exemplary embodiment of the invention;

FIGS. 11A-11G show nozzle designs, in accordance with exemplaryembodiments of the invention;

FIGS. 12A-12C illustrate an end-to-end anastomosis, in accordance withan exemplary embodiment of the invention;

FIGS. 13A-13D are side cross-sectional views showing embodiments where asupport is provided inside the blood vessels, in accordance withexemplary embodiments of the invention; and

FIG. 14 is a cross-sectional view of an adhesive anastomosis capsule, inaccordance with an exemplary embodiment of the invention.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Overview of Adhesive Anastomosis

FIG. 1 is a flowchart of a method of performing an adhesive-basedanastomosis, in accordance with an exemplary embodiment of theinvention. This flowchart is described below in conjunction with variousexemplary variations of adhesive based anastomosis.

FIG. 2A shows a “side” vessel 200, for example a coronary vessel,including an occlusion 202, for example partial or complete. In a bypassprocedure, a graft 204, for example a patent blood vessel, such as theITA (LIMA, RIMA), Radial, GEA, or a live graft, such as saphenous vein,a xenograft or an artificial graft is attached to the side of vessel 200at a point 206. In the example of a vessel other than the LIMA and RIMA,the other end of the vessel may be connected to a source of blood, suchas the aorta or the other side of occlusion 202. While not essential, inan exemplary embodiment of the invention, the attachment is a side (ofvessel 200) to end (of graft 204) attachment. Unless otherwisespecified, the terms blood vessel and graft are used interchangeably inthis specification and its claims. However, it should be noted that theadhesion properties and resistance to transfixing and cutting isdifferent for different types of blood vessels and grafts and may affectvarious device parameters.

Procedure Preamble

There are many clinical indications for the need to do an anastomosis,for example damaged blood vessel, clogged or stenosed blood vessels andorgan or tissue implantation. For clarity, the example used herein isthat of anastomosis as part of a coronary bypass procedure,specifically, anastomosis of a LIMA or RIME to a coronary artery, at apoint below occlusion 202. However, the scope of the invention is not tobe limited solely to methods and apparatus for these particularprocedures and is applicable to other anastomosis procedures.

Depending on the particular procedure and the situation of the patent,the location at which the anastomosis is to be made, is selected (102).In addition, various approaches to the site may be used. For example, aheart can be reached by opening the chest and spreading the ribs.Alternatively or additionally, the heart can be reached using a keyholeapproach with flexible or rigid tool. Alternatively or additionally, atransvascular approach may be used. Various apparatus suitable for thesedifferent approaches are described below.

Preparation (103)

A blood vessel is typically covered with various tissue layers, some ofwhich may not be compatible (e.g., adhere well) with the adhesive used.Alternatively or additionally, some of the layers may be incompatiblewith a patent connection, for example, not being sealed to blood ornaturally flaking. For example, an adventisia layer may not attach wellto an intima layer. Alternatively or additionally, one of the vessels isa non-living graft, for example, being made of polyester.

In an exemplary embodiment of the invention, the surface of one or bothof the target vessels (e.g., near where adhesive is expected to beapplied) is prepared, for example by cleaning, drying or applying aprimer. Exemplary primers include a setting enhancer, a coagulationenhancer, a fibrin layer and/or bio-active materials which affect thehealing and/or surface characteristics (e.g., pore opening) of thetarget tissue. Alternatively or additionally, such preparation isprovided later, for example as described below. Alternatively oradditionally, the anastomosis area may be washed, for example using asaline solution, optionally provided from one or more of the adhesivenozzles (described below).

Blood flow to one or both of the vessels may be stopped (if it exists)prior to incision, for example, using clamps. Alternatively, flow in atleast the side vessel is allowed during the anastomotic procedure, forexample, by covering the incision with a finger and then quicklyinserting vessel 204 into the incision, possibly covering the incisionwith a finger in the mean-time.

Incision (106)

Typically, an aperture needs to be formed in one or both of the targetvessels (104). In an exemplary embodiment of the invention, an incisionis formed. Exemplary systems for forming openings (e.g., by cutting orpunching) in blood vessels are described, for example in PCTpublications WO 01/70090, WO 02/30172, WO 99/62415, WO 01/0091, WO01/41623, WO 00/56228, WO 02/074188, WO 02/47532, WO 02/47561, WO00/56226, to applicant ByPass inc., the disclosures of which areincorporated herein by reference. Other arteriotomes are known as wellin the art and may be used. In some embodiments of the invention, othermeans, such as laser cutters are used to form openings. The incisionforming device may be separate from the adhesion device. Alternatively,they may be integrated. For example, a single delivery tube may be usedselectively for providing a hole punch or vessel cutter and thenproviding a graft mounting system. Optionally, incisions are used forsmaller vessels and punching is used for larger vessels.

FIG. 2B shows vessel 200 (in side view) with an incision 208 formedtherein, and an exemplary cutter 210 suitable for forming such anincision. Cutter 210 is optionally provided through a delivery system212, for example a flexible or rigid tube. Alternatively to forming anincision, a hole may be punched. In an exemplary embodiment of theinvention, the punch of PCT publication WO 99/62415 is used, which punchforms a seal in the blood vessel. Also, this punch allows the punchingelement to be removed and a graft delivery system provided, withoutsignificant leakage of blood.

While an end vessel does not generally need an incision, somepreparation may be provided, for example ensuring the angle of thevessel is suitable or cutting off ragged parts.

Mounting (104)

FIG. 2C shows vessel 204 mounted (104) in a graft delivery system 220,which may itself be provided via tube 212 (shown in 2B), in accordancewith one exemplary embodiment of the invention. In the particularexample shown, vessel 204 is partially everted or flared over a lip 222.In an exemplary embodiment of the invention, lip 222 comprises aplurality of lip elements that jut radially inwards from a tip of adelivery tube 228, thus allowing adhesive to flow between the elements(e.g., lips 222 may be formed as a slotted ring). Also shown are one ormore nozzles 226 for providing an adhesive which flows through a volume224 defined between the graft and delivery tube 228. In an exemplaryembodiment of the invention, tube 228 prevents adhesive from spillingout of the anastomosis area, for example as will be described below.

Also shown are a plurality of pullers 230 which serve to hold vessel 204in place and/or to assist in flaring of vessel 204, it should be notedthat in some embodiments of the invention, vessel 204 is not everted.Alternatively or additionally, if a temporary connector is provided, theconnector itself may hold the graft, for example as described in theabove applications. Alternatively or additionally, lip elements 222 mayinclude barbs (not shown) to hold vessel 204. FIG. 3 shows a graftdelivery system 300 in accordance with an alternative embodiment of theinvention, in which a plurality of suction elements 302 together holdthe tip of vessel 204. This type of suction system may be used foranastomosis methods that do not use adhesives, as well. Suction istypically provided by suction sources or by a wall socket in operatingrooms.

Returning to FIG. 2C, also shown are a plurality of pullers 232 whichare optionally used for guiding vessel 204 to vessel 200 and/or forwidening incision 208. PCT publications WO 01/41624, WO 01/70090 and WO02/30172, for example, the disclosures of which are incorporated hereinby reference, describe anastomosis system delivery systems includingone, two or more sets of pullers. In some embodiments of the invention,an anastomosis connector is provided to hold together the blood vesselsand the adhesive serves as a sealant and possibly for strengthening.Alternatively or additionally, the connector is used to hold the vesselstogether and then removed. One suitable removable connector is a clipring shown in FIG. 4 of PCT publication WO 01/70090, which may becoupled to the delivery system, for example by welding. This clip ringcomprises a ring having fingers extending away from the ring in a mannerwhich allows the delivery system to close the fingers from outside theblood vessel in the shape of clips. The ring is optionally split, toassist removal.

In an exemplary embodiment of the invention, vessel 204 is mounted bypulling vessel 204 through an aperture 234 in the side of graft deliverysystem 220. An exemplary pulling system is shown in PCT publication WO01/70118, the disclosure of which is incorporated herein by reference.Then, pullers 230 are loosened and placed on the tip of vessel 204, forexample manually or using tweezers. Pullers 230 are then tightened, forexample by retraction of a puller retractor 236, completing themounting.

Approximation (110)

Vessel 204 is guided to a correct alignment with vessel 200, the termjuxtapose (and juxtaposition) are also used herein as the process (andstate) where two blood vessels are positioned one near another in aconfiguration. Guiding may be by manipulating pullers 232. Alternativelyor additionally, guiding is directly manual, for example holding andmoving one or both vessels by hand or using a tool which is a directextension of the hand, such as forceps or manipulating a guide tube thatholds a vessel, thereby being a direct extension of the vessel. FIG. 2Dshows pullers 232 extended and inserted into incision 208. In anexemplary embodiment of the invention, approximation includes openingincision 208 so that some of delivery system 220 and/or vessel 204 mayenter. Opening the incision may be achieved automatically by retractingpullers 232. For example, an optional apertured ring 207 may beprovided, which urges pullers 232 apart. Alternatively or additionally,one or more external arms (not shown) may be used to selectivelyradially separate pullers 232.

PCT application PCT/IL02/00790, the disclosure of which is incorporatedherein by reference describes a hook guide which may be used to guidethe tips of pullers 232 into incision 208. In brief, the guidecomprises, in one embodiment thereof, a tube slotted along its lengthwith a flared end and a pointed end and having an inner lumen sufficientto receive the tips of pullers 232. The pointed end is placed intoincision 208 and then the tips of pullers 232 are guided into the tube,along the slit, using the flaring for assistance. The bodies of pullers232 remain outside the tube and pass through the slot into the tubelumen. When the puller tips are inside incision 208, the tube isremoved.

Final Arrangement (112)

When pullers 232 are retracted as compared with the side vessel, the twovessels are arranged and, optionally, are not allowed to move relativeto each other until after the adhesive is set. FIG. 2E shows vessels 200and 204 in the final arrangement configuration and prior to applicationof adhesive. In addition, in the embodiment shown, pullers 232 alsowiden incision 208, as they extend radially. As shown, the pullers arenot retracted enough to contact the intima of vessel 200 to the intimaof vessel 204, however, in other embodiments this may be done.Similarly, while vessel 204 is partially-everted/flared to expose itsintima, in some embodiments, it is not

In some embodiments of the invention, a temporary anastomotic connectoror clip(s) is used to perform this final arrangement. The connector maythen be removed or dissolve on its own, for example. In otherembodiments, the stabilization of the blood vessels is provided bymaintaining the pullers in a fixed configuration. In some cases, if thepullers are moved, the vessels move away from arrangement.

Scaffolding (108)

Alternatively or additionally to using a suitable delivery system, othermethods may be used to bring vessels 200 and 204 to the situation ofFIG. 2E. In an exemplary embodiment of the invention, scaffolding ismounted on one or more of vessels 200 and 204 and then used forapproximation and/or attachment.

FIGS. 4A-4E illustrate hook-based scaffolding, in accordance with anexemplary embodiment of the invention. FIGS. 4A and 4B sidecross-sectional views showing the mounting of a plurality of scaffoldwires 402 and 404 on vessels 204 and 200, respectively. FIGS. 4C and 4Dare perspective views of vessels 204 and 200, respectively. FIG. 4E is aside-cross-sectional view showing vessels 200 and 204 afterapproximation and attachment. After the anastomosis is completed, thescaffolding is removed, for example, by pulling, as described below.

The scaffolds may be manipulated, for example, by hand or using simpletools such as pliers, for mounting and movement of the blood vessels.Alternatively, the scaffolds may be mounted onto a guidance system, forexample a system 410 shown in FIG. 4E. The mounting may be performed,for example after the scaffolds hook onto the vessels. System 410comprises generally of a tube, having a flaring tip 412 with a rim atone end thereof, which rim defines one or more slots or apertures tohold the scaffold wires, when the wires are bent back towards the otherend of system 410. An engagement ring (not shown) may be used toselectively pull back some or all of the scaffold wires and/or to holdthem in place. Such a ring may be, for example, an elastic band on thetube.

FIGS. 5A-5C illustrate adhesive-based scaffolding, in accordance with anexemplary embodiment of the invention. FIGS. 5A and 5B arecross-sectional views of scaffold wires 502 and 504 mounted usingadhesive dabs 506 to vessels 204 and 200 respectively. This scaffoldingmay be mounted, for example by hand, optionally by applying one or moresuture. Alternatively or additionally, a scaffold delivery system isprovided, for example, a tube coated with an adhesive layer (not shown),with the scaffolding mounted on its end, possibly a thick tacky layerwhich optionally does not dry. After the scaffolding is contacted tovessel 200, the tube is removed, leaving the scaffolding. The tube isoptionally protected against inadvertent contact with nearby tissues, byan outer tube.

It should be noted that in different embodiments, the acts of mounting(104), incision (106) and scaffolding (108) may be applied in otherorders.

In an exemplary embodiment of the invention, the scaffolding of vessel200 is then attached to delivery system 220. Optionally, this allows thescaffolding to be used, by the delivery system, for guidance and/orattaching the vessels.

While the scaffolds are shown as uncoupled wires, this is not essential.For example, the scaffold may comprise an apertured ring (not shown)through which apertures the wires pass and which contacts one or bothblood vessels when the vessels are attached.

In an alternative exemplary embodiment of the invention, the scaffoldingcomprises one or more sutures, which may then dissolve or be pulled out,after their function is completed, for example.

Pre-Adhesion (114)

In an exemplary embodiment of the invention, before an adhesive isapplied, the anastomotic area may be prepared (114), for example, byproviding a primer as described above. One way of applying a primer isusing the adhesive applicator described below in FIG. 6. Alternativelyor additionally, the anastomotic area may be dried, for example byapplying a stream of gas.

Adhesion (116)

FIG. 2F shows an adhesive material 240 being applied to the anastomoticarea (116), in accordance with an exemplary embodiment of the invention.While the term adhesive is used, various embodiments of the inventionutilize different bonding and sealing effects. For example, the adhesivemay be provided outside the blood vessels to seal in any blood and/or tomaintain the two vessels in correct approximation. Alternatively oradditionally, the adhesive may fill cracks in the contact area betweenthe vessels. Alternatively or additionally, the adhesive may serve toattach the two vessels together, for example being applied to one orboth vessels prior to their being contacted or being injected into thecontact points. In an exemplary embodiment of the invention, theadhesive used is one or more of Coseal, a binary sealant formed of twopolyethylene glucol polymers, Costatis or Dynastat, by CohesionTechnologies, inc. (Palo Alto Calif.), Floseal, a collagen based matrixby Fusion medical technologies, inc. (Fremont Calif.), Tisseel, a fibrinsealant by Baxter (Deerfield Ill.), Hermaseel, by Haemacure (Kirkland,Canada), Cryoseal FS system by Thermogenesis (Rancho Cordova Calif.) andBioGlue, by Cryolife Inc. (Atlanta Ga.).

In the embodiment shown in FIG. 2F, the adhesive is provided via one ormore nozzles 226. In an exemplary embodiment of the invention, nozzles226 are used to provide a certain even or uneven distribution.Alternatively or additionally, if complex adhesive compounds are used,they may be mixed on site, for example, with different nozzles providingdifferent components. Alternatively or additionally, the adhesives maybe mixed before they exit the nozzle, for example in the nozzle orbefore the nozzle. Alternatively or additionally, one or more of thenozzles is used to provide an aggregate material, for example, fibers,to strengthen the anastomosis connection. In the embodiment shown, asplit nozzle is used, which includes a slot 227 for receiving vessel204.

Optionally, a frame, for example, a thread or a ring 242 is provided atthe anastomosis location, for example, to assist in strengthening theadhesive or to assist in sealing the anastomosis. It should be notedthat this frame on its own cannot form a patent anastomosis, and in someembodiments, is not attachable to blood vessels, except using adhesive.

FIG. 6 is a schematic illustration of an adhesive delivery system 600,in accordance with an exemplary embodiment of the invention. System 600comprises a tube body having a splittable aperture 604, defined at itsdistal end, for passing vessel 204. A plurality of pullers 232 forpulling vessel 200 are shown extending form the distal end as well. Inthe embodiment shown, a pistol-grip 606, with a lever 608 for retractingpullers 232, is shown. In an exemplary embodiment of the invention, aknob 610 is provided for injecting adhesive, a scale for showing theamount of such injection 612 is optionally provided.

In an exemplary embodiment of the invention, the amount of adhesiveapplied is measured beforehand, for example, provided in a capsule offixed and known size, for example as a collapsible capsule for example,underlying or in place of scale 612. Alternatively or additionally, thetip of system 600 is replaceable, for example as described in PCTapplication PCT/IL02/00790 and PCT publication WO 02/30172, thedisclosures of which are incorporated herein by reference. In anexemplary embodiment of the invention, this tip includes an adhesivecompartment. A replaceable tip capsule is described below in FIG. 14.

Alternatively, the lever is used for adhesive application and the knobfor puller retraction. In an alternative embodiment of the invention, ahydraulic system is used for controlling the pullers and the adhesiveapplication. A hydraulic system which is suitable (with appropriatemodifications) is described in a US provisional application filed onNov. 12, 2003, by inventor Amir Loshakove, et al., having the title“PRESSURE POWERED ANASTOMOTIC SYSTEM” and having attorney docket number[088/03773], the disclosure of which is incorporated by reference. Insuch a hydraulic system, a piston and cylinder mechanism is used inwhich fluid entering a chamber defined by the piston and the cylinderbody causes motion of one or both of the cylinder body and piston,thereby acting like a retraction force on a capsule.

FIG. 7 shows an adhesive delivery system including an optional rim 702which prevents spillage of adhesive out of the anastomotic area and/orshapes the geometrical distribution of the adhesive to a shape 704.Various rim shapes may be provided. The pullers are not shown, forclarity and may be contained, for example, in suitable slits and/orapertures.

Alternatively or additionally, to a rim, a separate form may be used.This form may be, for example, selected or distorted to match theparticular anastomotic situation. Optionally, there is no openingsbetween the form (or rim), the delivery system and the blood vessels, sothat the anastomotic area can fill with adhesive and possible bepressured above atmospheric pressure by the nozzles.

In an exemplary embodiment of the invention, the inside of the deliverysystem is coated with or formed of a material which does not bond to theadhesive. However, in a one time use system this is not essential.

In an exemplary embodiment of the invention, the adhesive is provided inone or more sequential portions. Optionally, the delivery system ismanipulated between sequential portions. In one embodiment of theinvention, tube 228 is retracted after a first portion of adhesive isapplied. In another embodiment, pullers 230 are retracted after a firstportion of adhesive is applied, to pull vessel 204 into an area in whichthere is adhesive and/or ensure that there is a layer of adhesivebetween the vessels. Optionally, any adhesive that enters the bloodvessels is washed away and diluted by the blood flow.

Alternatively to providing the adhesive as a fluid, it may be providedas a foam, for example using a foaming chamber (not shown) to convertfluid adhesive into a foam, for example using a gas source. Various gassources are typically provided in operating rooms, including nitrogen,oxygen and carbon dioxide. Alternatively a dedicated canister may beprovided. Alternatively, the adhesive is provided as a spray, forexample, using an atomizing nozzle.

Optionally, the adhesive includes a clot-inducing material, or ahealing-related material, or one may be provided as a primer.

While the adhesive is applied by a delivery system in exemplaryembodiments of the invention, alternatively, the adhesive is applied byhand, for example being pre-applied to one or both of the vessels and/orapplied using a syringe-like element.

Pre-Setting (118)

Prior to the adhesive setting (118), one or more acts are optionallycarried out. In one example, excess adhesive is removed, for example bywashing or by picking.

Setting (119)

During the setting time, heat, pressure and/or vibration are optionallyapplied to the adhesive, for example using delivery system 220 or aseparate device, to assist in proper and/or rapid setting of theadhesive.

In an exemplary embodiment of the invention, heat is applied byproviding an adhesive with small bubbles and applying ultrasonicradiation to the adhesive, to cause cavitation. Alternatively oradditionally, one or more conducting wires are provided in the adhesiveand which serve to receive RF radiation and heat by eddy currents.

In an exemplary embodiment of the invention, hot or unheated gas isblown through nozzles 226 or through a different set of nozzles. Coldgas is optionally used to reduce local blood flow. Alternatively oradditionally, a separate device is used to blow the gas. In an exemplaryembodiment of the invention, the gas is heated using an electricalheating element. The gas source may be, for example, a standard gassource as found in hospital rooms. Alternatively, a separate canistermay be provided. Such a gas source may also be used for drying, forexample as described above.

Optionally, gas blowing is used to blow away blood from leaks, thuspossibly assisting in carrying out the procedure without blocking bloodflow in vessel 200.

Blood flow (if blocked) may be enabled, for example, once the adhesivehas sufficiently hardened (e.g., to bond and/or seal) and/or if theattachment (without adhesive) is strong enough. In some cases, bloodflow may prevent adhesive from hardening inside the blood vessels.

Post-Setting (120)

While adhesive often asymptotically sets over a long period, a majorportion of the setting is often completed within a short time, forexample, 1 minute. After this time, the anastomosis may be considered tobe “completed” for all or most intents.

Various methods may be provided for determining that the adhesive isset. In an exemplary embodiment of the invention, the adhesive hardens,which may be felt by manual manipulation. In another embodiment of theinvention, a set time is allowed to pass before the procedure isconsidered to be completed. Optionally, the delivery system includes anelectronic or mechanical timer, with an audio and/or visual alert toindicate the set time is over (e.g., indicated as an element 614 on FIG.6). In another embodiment of the invention, the adhesive includes acompound or element that changes color or other optical properties suchas diffusion or transparency, when the adhesive sets. Alternatively oradditionally, a timer (e.g., electronic, mechanical or chemical) isinserted into the anastomosis area. Alternatively or additionally, amarker is inserted into the adhesive and is released by the setting ofthe adhesive. Optionally, one or more of pullers 230 or 232 serves as amarker, being coated for example with Teflon, to prevent adhesion.

Optionally, the delivery system is maintained at the anastomosislocation until the adhesive is set. In an exemplary embodiment of theinvention, a sensing method is used to determine the setting status, forexample, by sensing electrical conduction or capacitance propertiesand/or using a pressure sensor (sensors not shown, but are provided forexample near the nozzles).

Optionally, the anastomosis area is shaped, for example by removingexcess adhesive and/or smoothing any sharp edges inadvertently formedduring or after setting.

Scaffold Removal (122)

In some embodiments of the invention, the scaffold dissolves or isabsorbed after a while. Alternatively, the scaffold may be kept in thebody. Alternatively, the scaffold is removed, to reduce the existence offoreign materials in the body. In an exemplary embodiment of theinvention, the scaffold parts are simply pulled away from the vessels.Optionally, the scaffold is heated or vibrated, to assist in removal.

FIG. 2G shows a completed anastomosis, in accordance with an exemplaryembodiment of the invention, including an adhesive section 250, and inwhich the pullers were retracted so that the two vessels touch tip totip.

Optionally, if the scaffold hole leaks, more adhesive is applied.Alternatively or additionally, compression is applied until the leakingblood clots.

In an exemplary embodiment of the invention, the delivery system is asplit system, for example as described in PCT publication WO 00/56226,the disclosure of which is incorporated herein by reference, in which issplit for removal from vessel 204.

Post-Procedure (124)

After the anastomosis procedure is completed, a check for leaks isoptionally performed (any leaks are optionally corrected by applying adab of adhesive) and the entry port is closed. After a period of time,the adhesive optionally dissolves or is absorbed, leaving no foreignmaterials in the body, in accordance with some embodiments of theinvention.

Exemplary Adhesive Materials

A wide range of adhesive materials may be used for the above describedembodiments. In some cases, the delivery system will be modified, forexample, to account for differing viscosity, drying times, primersand/or drying enhancers suitable for each adhesive. In an exemplaryembodiment of the invention, the adhesive is selected to dissolve orotherwise dissipate after between 1 day and 2 weeks, for example,between 3-7 days. In some types of adhesives, the tissue grows into oraround the adhesive, mooting the need for an adhesive. For example,matrix type adhesives tend to encourage tissue grows into the matrix.Alternatively, the two blood vessels are contacted and at the contactpoint tissue adhesion or ingrowth occurs. Optionally, no adhesive isprovided at those points, for example, by first contacting the vesselswith a minimum force to ensure good contact and then applying adhesive,which does not flow between the contact surfaces. In other embodiments,the adhesive is of a type that flows between contact surfaces or thecontact pressure is low enough to allow such flow in a regular adhesive.

Approximation Geometries

The lips of the two vessels may be arranged in various ways, each ofwhich may have utility for certain situations and/or conditions, forexample, one or more of the following considerations may be relevant:

(a) minimizing non-intima surfaces may provide best blood interface;

(b) minimizing stretching of vessels may prevent tears and/or distortionof an anastomosis area during and after procedure;

(c) maximizing contact area between vessels may reduce leaks or enhancestrength; and

(d) laying out of vessels in a manner which minimizes contact (or makesit easier to minimize) between the anastomosis area and nearby tissueduring the setting period.

In contrast to general anastomotic connectors, in an exemplaryembodiment of the invention, some freedom of approximation configurationis provided by the adhesive optionally sealing in the entire anastomosisarea, possibly relieving strain, preventing leaks and/or strengtheningthe connection between the blood vessels.

Optionally, a single delivery device is used to provide multiplearrangements, for example, based on how far and/or relative retractionof pullers and/or based on how scaffolds are mounted on the bloodvessels.

In the example of FIG. 2, the relative positions of the two bloodvessels can optionally be controlled by selectively pulling back more onone or the other of pullers 232 and 230. Optionally, the handle of thedelivery system includes one or more settings for relative positions ofthe two sets of pullers, when retracted.

FIGS. 8A-8E show various attachment configurations of blood vessels, inaccordance with exemplary embodiments of the invention. FIG. 8A shows anintima-to-intima connection. FIG. 8B shows another intima-to intimaconnection, in which vessel 200 is everted more and vessel 204 less,than in FIG. 8A. FIG. 8C shows a configuration where the lips of vessel200 are inserted inside vessel 204. FIG. 8D shows an embodiment, whereonly vessel 204 is everted and only a small amount (alternatively, noeversion is provided). FIG. 8E shows an embodiment where vessel 204 isinserted into vessel 200.

FIGS. 9A and 9B show an exemplary method of achieving the configurationof FIG. 8C, in accordance with an exemplary embodiment of the invention.In this embodiment, two or more pullers 902 are provided through one ormore matching apertures 904 that are formed in vessel 204. FIG. 9B showshow vessel 200 is engaged on its inside by pullers 902. When pulled, theconfiguration of FIG. 8C results. The holes left by pullers 902 invessel 204 may be self-sealing. Alternatively or additionally, a dab ofadhesive is applied. Alternatively or additionally, an adhesive patch isapplied. A patch of vascular tissue or other material is provided overthe anastomosis area, in some embodiments of the invention.

FIGS. 10A and 10B show an exemplary method of achieving theconfiguration of FIG. 8E, in accordance with an exemplary embodiment ofthe invention. A plurality of pullers 1002 penetrate through a wall ofvessel 200 and engage vessel 204, after it is inserted into incision208, from the inside. In an exemplary embodiment of the invention,pullers 1002 are pre-stressed to be bent and are inserted using aplurality of over-tubes 1004. During insertion puller 1002 is completelyenclosed by the over tube except for its tip. This tip penetrates vessel200 and then, as it is extended from overtube 1004, curls and engagesvessel 204. Optionally, a contra (not shown), for example a slotted tubeprovided over vessel 204 is used to maintain vessel 204 open and assistin penetration of pullers 1002 into vessel 204. In FIG. 10B, pullers1002 are retracted, so that they straighten and flare vessel 204 asshown. If retracted a small amount, vessel 204 will be partiallyeverted/flared and vessel 200 not everted. If pulled back more, aconfiguration similar to that of FIG. 8E will result.

Thus, FIGS. 9 and 10 show that a single set of pullers can be sufficientfor approximation and attachment. It should be noted that by utilizing aflared element such as shown in FIGS. 4E or 5C, the pullers can beretracted in various directions and amounts. While pullers arementioned, similar methods can be applied for scaffolds of varioustypes.

In some embodiments of the invention, the pullers are pre-bent and/orpre-strained (e.g., for super elastic elements) by hand or machine tomatch a desired angle of the anastomosis.

Nozzle Designs

FIGS. 11A-11G show nozzle designs, in accordance with exemplaryembodiments of the invention, of which, FIGS. 11A-11C show nozzle setdesigns.

FIG. 11A is a front view of a nozzle set 1100, in which a ring shapedcanister 1102 (optionally elongated like a cylinder) defines a pluralityof nozzles 1104 for providing adhesive or other materials. Vessel 204(not shown) optionally passes through the hole of the ring. A slottedring may be provided (not shown) with the vessel fitting through theslot.

FIG. 11B shows an alternative nozzle set 1110, in which two separatearcuate shapes 1112 each define a plurality of nozzles 1114. Optionally,each shape 1112 is used for delivering a different material.Alternatively or additionally, each shape may be positioned at adifferent axial position and/or may be controlled separately, forexample, to have different adhesive extrusion rates.

FIG. 11C shows a nozzle set 1120, in which a plurality of nozzles 1124are each fed by a separate tube (not shown).

A mixture of different nozzle arrangements may be provided as well.Where a single nozzle is used for delivering a plurality of fluid types,the nozzle may include a switch (not shown) for switching betweendifferent sources. Different nozzles may have different shapes, types,locations (axial), angles (to the device axis), sources, material and/orpressure feed. For example, a set of nozzles may include alternatingadhesive and setting material nozzles.

FIGS. 11D-11G show individual nozzle designs in accordance withexemplary embodiments of the invention.

FIG. 11D is a cross-sectional view of a nozzle 1130, having a mixingarea 1132 and a pre-exit narrowing 1134. A flare 1136 is provided, whichmay, for example as shown, curl back. This may assist in forming theadhesive into drops.

FIG. 11E shows a mixing nozzle 1140, in cross-sectional view. A mixingarea 1142 includes a plurality of threads or baffles 1144, which causeturbulence and mixing of the material in the nozzle.

FIG. 11F shows a watering-can like nozzle 1150 in side cross-section andfront views. The nozzle comprises a mixing area 1152 and a front plate1154 defining a plurality of apertures 1156 (shown in frontal view1151).

FIG. 11G shows a paired nozzle 1160, in which two arc-profile lumens1162 and 1164 are provided. Nozzle 1160 may be solid at its center orhollow as shown. In an exemplary embodiment nozzle 1160 is large (asshown for example in a front view 1161) enough to include a vessel atits center, in which case one or more slots may be provided forreceiving the vessel.

Exemplary End-to-End Embodiment

FIGS. 12A-12C illustrate an end-to-end anastomosis, in accordance withan exemplary embodiment of the invention. In this embodiment, two endvessels 1206 and 1208 are attached end to end. Each vessel is mounted onits own delivery system, 1202 and 1204 respectively, which areoptionally adapted to interlock, for example, by an inner tube 1210 ofdelivery system 1202 fitting inside an outer tube 1212 of deliverysystem 1204. Other interlocking mechanisms may be used as well. A fixingmeans, for example threading, friction or a clasp, are optionallyprovided.

In the embodiment shown, the vessels enter through the side of thedelivery systems and pullers 1214 and 1216 are provided for everting thevessels, as shown in FIG. 12B. Knobs 1218 and 1220 are optionallyprovided for retracting the pullers. Adhesive is optionally provided byonly one of the systems, for example, system 1204, using a lever 1222,for example.

FIG. 12B is a side cross-sectional view, showing systems 1202 and 1204interlocked and showing the vessels retracted and everted by thepullers, so that they contact intima-to-intima Also shown is provisionof adhesive 1230 via a plurality of channels 1232 to an anastomosisregion 1234 which is defined by the interlocking systems.

FIG. 12C shows the end result of the anastomosis, in sidecross-sectional view.

A similar system can be used for side to side or side to endconnections. A portion that holds a side vessel will generally not berotationally symmetric, however.

Internal Support Embodiment

FIGS. 13A-13D are side cross-sectional views showing embodiments inwhich a support is provided inside the blood vessels, alternatively oradditionally to using scaffolding and/or pullers during the applicationof adhesive. The shown structures are optionally provided through a holein one or both vessels, which may then be closed, for example with atissue patch, with a closure device or with a suture. In an exemplaryembodiment of the invention, existing or modified bypass shunts areused. Such shunts are sold for example under the trade name Flo-Through,by Bio-Vascular Inc., which also sells occluders, under the nameFlo-Rester.

In FIG. 13A, a light collapsible structure 1302 is provided, which, whenretracted, can be pulled out through end vessel 204. Since thisstructure only provides some support during the anastomosis procedure,it is generally not required to be strong. As shown, a lumen 1308, whichmay be used to shunt blood is provided. Alternatively, no lumen (andthus no blood flow) is provided. In an exemplary embodiment of theinvention, an area 1310 of the structure which is near the anastomoticlocation, is substantially in contact with the location (not as shown,for clarity), to provide support for the anastomosis area. In standardshunts and occluders, such contact may be undesirable, as it increasesdevice size and may interfere with manipulation of the vessel (orsutures). It should also be noted that in some embodiments of theinvention blood flow near the anastomosis location is allowed before,during and/or after the adhesive is applied, so a complete seal of thedevice (e.g., of one or both lips 1307 thereof) to the vessel walls isnot required in these embodiments and unlike a shunt or occluder.

In FIG. 13B, two separate elements are provided, a light structure 1306(e.g., shunt or occluder) which may be retracted through a hole in sidevessel 200 and a tube 1304 which is retracted through vessel 204 (andmay support vessel 204 during anastomosis). Optionally, structure 1306is retracted and collapsed into tube 1304, for removal.

In FIG. 13C, a single, T-shaped balloon 1310 provides support.

In FIG. 13D, a regular balloon 1314 is used for support, with vessel 200acting as a continuation of vessel 204 after the anastomosis. Possibly,one branch of vessel 200 is sealed by the anastomosis, but this is notessential, for example if a wall 1316 of vessel 204 continues intovessel 200.

In some embodiments of the invention, the structures of FIGS. 13A-13Dare fixedly coupled to the adhesive delivery system, for example byproviding suitable jaws (not shown) on the delivery system.

Automation and Feedback

In an exemplary embodiment of the invention, the adhesive deliverysystem is provided with various automatic features (some of which aredescribed above), for example, one or more of:

(a) providing feedback on setting of adhesive, on heating of adhesiveand/or on drying of anastomosis area;

(b) safety features, such as some controls being active only after aprevious control was used, for example, adhesive flow being enabled onlyafter puller retraction;

(c) electrical power instead of manual power, for example for adhesiveinjection, for example, to reduce jumping and/or provide finer controlover adhesive flow; and

(d) passage of time indicator(s).

The linkage between controls may be, for example, electrical.Alternatively or additionally, the linkage is mechanical, for example,retraction of pullers freeing a pin that allows an adhesive provisionlever to be moved.

Capsule Embodiment

PCT/IL02/00790 and WO 02/30172, the disclosures of which areincorporated herein by reference, describes a capsule based deliverysystem in which a removable capsule is attached on a delivery system andthe capsule includes both a connector and a mechanism for deploying thatconnector. FIG. 14 shows a variation of such a capsule 1400, incross-sectional view, showing the integration of an adhesive deliverysystem into such a capsule. The connector, as shown may be deployed bythe capsule, in one embodiment of the invention. In an alternativeembodiment of the invention, which may be preferred, for example sincefewer foreign materials are left in the body, the connector may be usedas mere scaffolding to be retracted with the system after the adhesiveat least partly sets.

Capsule 1400 comprises a forward end 1401 having an aperture 1402through which a vessel 204 enters end 1401, to exit from a frontaperture 1403. A plurality of pullers 230 are shown being an extensionof a base portion 1404 (which in an alternative design may be backwardspikes of an anastomotic connector). When a piston 1410 (or othermechanism) of capsule 1400 is retracted, a lever 1408 is retracted,which lever is coupled to a base 1406 on which base portion 1404 rests.This causes retraction of pullers 232. At the same time, a bladder ofadhesive 1416 is compressed between base 1406 and a narrowing 1412(which may be flared rather than stepped as shown) of capsule 1400.Adhesive is thereby forced to flow through tubes 1418 to deliverynozzles 1420, adjacent the anastomosis area.

As can be appreciated such capsule may be used for various types ofprocedural approaches, for example, open surgery, catheter basedsurgery, endoscopic surgery or keyhole surgery.

It should be appreciated that also a non-capsule delivery system may bemodified as described above to provide adhesive to an anastomosis area,for example in synchrony with retraction, as described, or at leastpartially independent of it, using a second lever.

Connector and Anastomosis Tools

As noted above, embodiments of the present invention may be used withvarious types of anastomotic connectors, anastomosis assisting tools anddelivery systems. In particular, the following documents, describeconnectors, delivery systems and/or other tools and methods which areuseful in conjunction with embodiments of the prevent invention:

PCT/IL02/00790, filed on Sep. 25, 2002, now published as WO 03/026475;

PCT/IL02/00215, filed on Mar. 18, 2002, now published as WO 02/074188;

PCT/IL01/01019, filed on Nov. 4, 2001, now published as WO 02/47532;

PCT/IL01/00903, filed on Sep. 25, 2001 now published as WO 02/30172;

PCT/IL01/00600, filed on Jun. 28, 2001, now published as WO 02/47561;

PCT/IL01/00267, filed on Mar. 20, 2001, now published as WO 01/70091;

PCT/IL01/00266, filed on Mar. 20, 2001, now published as WO 01/70090;

PCT/IL01/00074, filed on Jan. 25, 2001, now published as WO 01/70119;

PCT/IL01/00069, filed on Jan. 24, 2001, now published as WO 01/70118;

PCT/IL00/00611, filed on Sep. 28, 2000, now published as WO 01/41624;

PCT/IL00/00609, filed on Sep. 28, 2000, now published as WO 01/41623,

PCT/IB00/00310, filed on Mar. 20, 2000, now published as WO 00/56228;

PCT/IB00/00302, filed on Mar. 20, 2000, now published as WO 00/56227;

PCT/IL99/00674, filed on Dec. 9, 1999, now published as WO 00/56223;

PCT/IL99/00670, filed on Dec. 8, 1999, now published as WO 00/56226;

PCT/IL99/00285, filed on May 30, 1999, now published as WO 99/62408; and

PCT/IL99/00284, filed on May 30, 1999, now published as WO 99/62415. Thedisclosure of all of these applications, which designate the US and werefiled in English, are incorporated herein by reference.

In addition, the following PCT unpublished applications, all filed onSep. 25, 2003, in English and designating the US, the disclosures ofwhich are incorporated herein by reference describe tools and connectorswhich may be useful: PCT/IL03/00774, “Anastomotic Connectors”,PCT/IL03/00773, “Snare”, PCT/IL03/00770, “Sliding Surgical Clip”,PCT/IL03/00771, “Blood Vessel Cutter”, and PCT/IL03/00769, “AnastomoticLeg Arrangement”.

The following US provisional applications, the disclosures of which areincorporated herein by reference, also describe tools which may be ofuse, U.S. Ser. No. 60/492,998 filed on Aug. 7, 2003 and U.S. Ser. No.60/505,946, filed on Sep. 25, 2003 (in which an adhesive feature may beadded in accordance with an exemplary embodiment of the invention).

Some of these applications describe anastomosis delivery systems, holemaking apparatus and/or other connectors useful in cooperation with thepresent invention.

While the above delivery system has been described in general for anytype of blood vessel, it should be appreciated that particularmodifications may be desired for certain vessel types. For example, theaorta is thicker, while a coronary vessel is thinner, thus suggestingdifferent vessel holder sizes and/or puller geometries. For example, anaorta may be 3 mm thick, while a coronary vessel may be less than 1 mmthick.

It should be noted that the term “connector” should be construed broadlyto include various types of connectors, including one part, two part andmultiple part connectors, some of which when deployed, result in aplurality of individual clip-like sections.

The term “eversion”, where used means not only complete eversion of 180degrees, but also partial eversion or flaring, for example of 90degrees. Also, in some embodiments, mounting without eversion isprovided.

Measurements are provided to serve only as exemplary measurements forparticular cases. The exact measurements stated in the text may varydepending on the application, the type of vessel (e.g., artery, vein,xenograft, synthetic graft), size of connector, shape of hole (e.g.,incision, round) and/or sizes of vessels involved (e.g., 1 mm, 2 mm, 3mm, 5 mm, aorta sized).

While the term “tube” and other geometrical shapes have been describedand used for generality, it should be appreciated that this tube neednot have a full body nor have a circular cross-section, in someembodiments.

It will be appreciated that the above described methods of adhesiveanastomosis may be varied in many ways, including, changing the order ofsteps and the types of tools used. In addition, a multiplicity ofvarious features, both of method and of devices have been described. Insome embodiments mainly methods are described, however, also apparatusadapted for performing the methods are considered to be within the scopeof the invention. It should be appreciated that different features maybe combined in different ways. In particular, not all the features shownabove in a particular embodiment are necessary in every similarembodiment of the invention. Further, combinations of the abovefeatures, also for different embodiments, are also considered to bewithin the scope of some embodiments of the invention. Also within thescope of the invention are surgical kits which include sets of medicaldevices suitable for performing, for example, a single or a small numberof anastomotic procedures. In some embodiments, one or more of thedevices, generally sterilize, described above, are packaged and/or soldwith an instruction leaflet, describing the device dimensions and/orsituations for which the device should be applied. Section headingswhere are provided are intended for aiding navigation and should not beconstrued to limiting the description to the headings. When used in thefollowing claims, the terms “comprises”, “includes”, “have ” and theirconjugates mean “including but not limited to”.

It will be appreciated by a person skilled in the art that the presentinvention is not limited by what has thus far been described. Rather,the scope of the present invention is limited only by the followingclaims.

1. A method of performing an anastomosis, comprising: juxtaposing twoblood vessels to be anastomosed using an juxtaposition device, to adesired configuration in which at least one vessel is an end vessel;applying an adhesive to said vessels while they are in saidconfiguration, said adhesive being sufficient to ensure both sealing andbonding of said two vessels to each other; and removing saidjuxtaposition device after said adhesive sufficiently sets. 2.(canceled)
 3. A method according to claim 1, wherein juxtaposingcomprises inserting at least a portion of said juxtaposing device intoat least one of said vessels.
 4. A method according to claim 1, whereinjuxtaposing comprises inserting at least a portion of said juxtaposingdevice into a wall of at least one of said vessels. 5-17. (canceled) 18.A method according to claim 1, wherein applying comprises applying usinga plurality of nozzles arranged in a ring.
 19. A method according toclaim 1, wherein applying comprises applying into a mold adjacent saidanastomosis area, which mold shapes the adhesive about said area 20.(canceled)
 21. A method according to claim 1, wherein applying comprisesapplying a pre-measured amount of adhesive. 22-24. (canceled)
 25. Amethod according to claim 1, wherein said removing comprises removingbefore said adhesive sets completely.
 26. A method according to claim 1,wherein said removing comprises removing as soon as said adhesive startsto set. 27-28. (canceled)
 29. A method according to claim 1, wherein noforeign materials other than said adhesive remain in said anastomosis.30. A method according to claim 1, comprising providing at least onestrengthening element in said anastomosis and leaving said at least onestrengthening element permanently in said anastomosis.
 31. A method ofperforming an anastomosis, comprising: attaching at least a firstscaffold element to a first blood vessel; attaching at least said firstscaffold element or a second scaffold element to a second blood vessel;positioning said blood vessels using said at least a first scaffoldelement, to a desired configuration; applying an adhesive to saidvessels while they are in said configuration, said adhesive beingsufficient to ensure both sealing and bonding of said two vessels toeach other; and removing said at least first scaffolding element.
 32. Amethod according to claim 31, wherein said first blood vessel is a sidevessel.
 33. A method according to claim 31, wherein said first bloodvessel is an end vessel.
 34. A method according to claim 31, comprisingmechanically attaching said at least first scaffolding element to saidfirst blood vessel.
 35. A method according to claim 34, whereinmechanically attaching comprises piercing.
 36. A method according toclaim 34, wherein mechanically attaching comprises hooking. 37-40.(canceled)
 41. A method according to claim 31, wherein said at least onescaffolding element comprises a plurality of wires adapted to engage ablood vessel.
 42. (canceled)
 43. A method according to claim 31, whereinsaid at least one scaffolding element comprises a balloon. 44-50.(canceled)
 51. A method according to claim 31, wherein removingcomprises removing at least one of said at least one scaffoldingelements before said adhesive sets. 52-76. (canceled)
 77. An adhesiveanastomotic system, comprising: a first blood vessel holder; a secondblood vessel holder adapted to interlock with said first blood vesselholder, such that blood vessels held by said two vessel holders contact;and an adhesive port configured to deliver an adhesive to said contact.78-81. (canceled)